Project Summary

Miklos Toth, M.D., Ph.D. (Independent Investigator 2002) of Weill Medical College of Cornell University, has shown that a deficit in 5-HTA receptor, elicited by the inactivation of its gene, results in an anxiety-like phenotype in mice.  Extensive research revealed a remarkable parallel between the behavioral responses of receptor-deficient mice in stressful and challenging situations and the symptoms of human anxiety.  The aim of his current research is to specify molecular and cellular correlates of the 5-HTA receptor-deficit.  He speculates that specifying common expression changes among multiple anxiety-displaying mouse lines could help to find genuine “anxiety-specific” genes and will focus on screening a large set of genes (36,000) for possible alterations in 5-HT1A receptor-deficient mice.  He will then determine the mechanism responsible for altered gene expression, which could help to specify molecular targets for anxiolytic drug development, and then test if expression changes found in 5-HT1A receptor-deficient mice can also be found in three unrelated, genetically modified mice displaying anxiety phenotype.   This will allow him to identify anxiety genes whose altered expression is tightly associated with anxiety phenotype in the mouse.  If common anxiety-related genes are identified in multiple knockout mouse lines, than they can be viewed as functional candidates for susceptibility for human anxiety.  Then studies could be initiated to determine allelic variants of these genes and associate these variants with different forms of anxiety.

Program Area: ANXIETY DISORDERS

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